1. Field of the Invention
This invention relates to a process of stimulating and promoting the natural immune system (T cells and NK cells) resisting and inhibiting the growth of tumorous cells as well as resisting infections (virus, bacteria, and fungi). More specifically this invention relates to the in vivo use of leucine-enkephalin and methionine-enkephalin or the like.
2. Description of the Prior Art
Since the discovery, isolation and the complete analysis of the amino acid sequence of specific, endogenous, highly reactive and incredibly powerful peptides (e.g. interferon, endorphins and enkephalins), a rebirth and revitalization of interest and activity in biochemical research has taken place. During the last decade the industrial world's race to be the first to commercially synthesize interferon is not only a daily topic on Wall Street but is also well known to the layman and casual observer. Perhaps as at no other time in history has the phrase "the miracles of modern medicine" been more applicable as a geniuine expectation.
Consistent with the contemporary so-called `lock and key` theory, the existence of specific receptors in the brain for morphine-like substances has been established and corresponding endogenous specific ligands have been located and identified to be two pentapeptides, methionine-enkephalin and leucine-enkephalin (Hughes et al, Nature, 258 577-579 (1975); Simantov et al, Proc. Natl. Acad. Sci., U.S.A., 73 2515-2519 (1976); Kosterlitz, Opiates and Endogenous Opioid Peptides, Elsevier/North Holland Biomedical Press (1976)). Other larger peptides, the endorphins, have also been found to bind to morphine receptors (Li et al, Nature 260 622-24 (1976); Cox et al, Proc. Natl. Acad. Sci., U.S.A., 73 1821-23 (1976); Segal et al, Science 198 411-413 (1977)). Subsequent studies elaborated on the analgesic activity in various animal models by the intracerebral route of administration. However, there appeared to be a lack of analgesic activity when the peptides were administered by the intravenous (or intramuscular or intraperitoneal) routes of administration. This dichotomy of analgesic activity by different routes of administration (brain versus peripheral) was explained in terms of blood-brain barrier differences as well as a rapid rate of metabolism in plasma.
However, pronounced activity by systemic administration was discovered by Plotnikoff et al (Life Sci. 19 1283-1288 (1976)), who showed that the enkephalins-endorphins exhibited marked activity as tranquilizers and antidepressants. More important, Plotnikoff demonstrated that the enkephalins were extremely active in potentiating the central effects of dopamine.
In 1979, Wybran et al reported that normal human blood T lymphocytes bear surface receptor-like structures for methionine-enkephalin and recent discoveries further support the view that T-cell lymphocytes were covered with enkephalin and endorphin receptor sites.
In the same year, the New York Academy of Sciences Symposium on Subcellular Factors in Immunity (Volume 332, Dec. 28, 1979) disclosed that the thymus gland of animals and humans was secreting peptides (thymosin and others) that controlled activities of T-cell lymphocytes and associated cells. These thymus peptides were found to have anti-neoplastic effects in animals and humans. In addition, the thymus peptides were found to control the aging process. Finally, the thymus peptides appear to regulate `auto-immune responses` of lymphocyte particles.